Some plasma and saliva pharmacokinetics parameters of rifampicin in the presence of pefloxacin

The effect of pefloxacin on the pharmacokinetics parameters of rifampicin in humans was investigated using plasma and saliva concentrations. Five healthy volunteers (4 male and 1 female), ages 20-35 years, each received 600 mg rifampicin alone, and after a 1-week drug washout period, 600 mg rifampicin plus 500 mg pefloxacin was administered with 350 mL of water. Plasma and saliva concentrations of rifampicin were measured at 7 different time intervals and different pharmacokinetics parameters calculated. Pefloxacin coadministered with rifampicin reduced plasma and saliva elimination half-life, peak plasma concentration, area under the concentration time curve, volume of distribution, minimum absorption time, absorption rate constant, and absorption half-life showed a significant increase (P < 0.05). Time to reach peak plasma concentration was not affected with or without pefloxacin. Pefloxacin increases bioavailability of rifampicin and hence extends its detection in the body as demonstrated by rifampicin being estimated at 24 hours when coadministered with pefloxacin, whereas at 24 hours, it was completely absent when administered alone.     

Testicular toxicity of rinbacin in rats

Rinbacin is a local Nigerian herbal remedy. The effects of rinbacin on testicular histology were studied in prepubertal rats. Sexually immature male rats, divided into seven per group, were given rinbacin in drinking waters at 0, 26.25 g/l, or 52.50 g/l for 13 weeks, after which the animals were killed and testes excised, weighed, and processed for histologic study. The epididymal sperm number (ESN) was determined. There were no significant effects of either the low or high doses of rinbacin on fluid intake, body weight, testicular weight, and testis-body weight ratio. There was, however, a significant (p<0.05) decrease in the ESN of animals at both doses of rinbacin. Histologic examination of the testes indicated that the high dose of rinbacin induced significant degenerative changes, while the low dose had only a mild effect on testicular histology. Rinbacin decreases the ESN and causes degenerative lesions, especially at the high dose, in prepubertal rats.     

Lead poisoning associated with malaria in children of urban areas of Nigeria

The principal objectives of this study are to (a) investigate the prevalence of elevated blood lead levels (EBLLs) in children of three major cities of Nigeria with different levels of industrial pollution; (b) identify the environmental, social and behavioral risk factors for the EBLLs in the children; and (c) explore the association between malaria (endemic in the study areas) and EBLLs in the pediatric population. The study involved 653 children aged 2-9 years (average, 3.7 years). The mean blood lead level (BLL) for the children was 8.9+/-4.8mug/dL, the median value was 7.8mug/dL, and the range was 1-52mug/dL. About 25% of the children had BLL greater than 10mug/dL. There were important differences in BLLs across the three cities, with the average value in Ibadan (9.9+/-5.2mug/dL) and Nnewi (8.3+/-3.5mug/dL) being higher than that in Port Harcourt (4.7+/-2.2mug/dL). Significant positive associations were found between BLL and a child's town of residence (p<0.001), age of the child (p=0.004), length of time the child played outside (p<0.001), presence of pets in a child's home (p=0.023), but negatively with educational level of caregiver (p<0.001). This study is one of the first to find a significant negative association between BLL and malaria in a pediatric population, and this association remained significant after controlling for confounding diseases and symptoms. The shared environmental and socio-demographic risks factors for lead exposure and Plasmodium (most common malaria parasites) infection in urban areas of Nigeria are discussed along with possible ways that lead exposure may influence the host response to infection with malarial parasites.     

Immune response in demodicosis

BACKGROUND: Demodex folliculorum and Demodex brevis are obligatory parasites in the hair follicles and in the pilosebaceous glands. Although most people are infested with these mites, only a small number develop the clinical symptoms of demodicosis. The objective of this study was to determine the distinguishing features of the immune response to the infestation of the skin by Demodex mites. METHODS: Twenty-nine patients with human demodicosis and 13 age- and sex-matched healthy subjects participated in the study. The presence of mites was determined by microscopic inspection of secretion from sebum glands. The immune response was evaluated in the peripheral blood by identifying membrane markers of different immune cells using monoclonal antibodies, while the concentration of immunoglobulin (Ig)A, IgM and IgG was calculated by simple radial immunodiffusion using anti-IgA, anti-IgM and anti-IgG. The level of circulating immune complexes and total haemolytic complement, as well as the preparatory and digestive function of neutrophils, and the functional activity of leucocytes were also studied. RESULTS: The absolute number of CD95+ was higher in patients with demodicosis. The absolute number of CD3+, CD4+, CD8+ and CD16+ cells, the ratio CD3+/CD20+ and the functional activity of leucocytes were significantly lower in individuals infested with Demodex mites. No significant differences were found in the percentage and absolute number of CD20+ cells, the ratio of CD4+/CD8+ T-cell subpopulations, circulating immune complexes, level of serum complement activity (CH(50)), activity and index of phagocytosis and the levels of IgA, IgM and IgG antibodies between individuals infested with Demodex mites and the control group. CONCLUSION: The readiness of lymphocytes to undergo apoptosis increases in parallel to the increasing density of the mites. This could be the result of local immunosuppression caused by the mites, which allows them to survive in the host skin.     

Salivary and urinary excretion and plasma-saliva concentration ratios of isoniazid in the presence of Co-administered ciprofloxacin.

Salivary and urinary excretion and plasma-saliva concentration ratios of isoniazid (INH) in the absence and presence of ciprofloxacin (CP) were investigated in healthy female volunteers. Results obtained indicated an absorption form of interaction between INH and CP. This led to delay in gastric emptying and onset of absorption of INH in the upper part of the gastrointestinal tract, resulting in a corresponding delay in the onset of salivary and urinary excretion of the drugs. There was a 1-hour reduction in the time to attain peak saliva concentration of INH (tmax), an insignificant difference in peak saliva concentration (Cmax), and a significant (P = 0.05) increase in AUC(0-24h) of INH in the presence of CP. Cumulative amount of INH excreted in the urine increased approximately 38% in the presence of CP. The calculated plasma-saliva concentration ratios of INH were reduced in the presence of CP and were slightly lower than the experimental values. This indicates increased amount of the drug secreted into saliva in the presence of CP and possible buccal partitioning of the drug. Overall, results of the current study indicate that CP delayed the onset but not the extent of INH absorption. Therefore, concurrent administration of the two drugs was considered relatively safe, and the absorption interaction that may have occurred may not be of reasonable clinical consequence.     

Predictors of maternal mortality in institutional deliveries in Nigeria

Background

Maternal mortality in poor countries reflects the under-development in these societies. Global recognition of the burden of maternal mortality and the urgency for a reversal of the trend underpin the Millenium Development Goals (MDGs).

Objective

To determine risk factors for maternal mortality in institutional births in Nigeria.

Method

Twenty one health facilities in three states were selected using stratified multi-stage cluster sampling strategy. Information on all delivered mothers and their newborn infants within a three-month period was culled from medical records.

Results

A total of 9 208 deliveries were recorded. About one-fifth (20.5%) of women had no antenatal care while 79.5% had at least one antenatal visit during pregnancy. Four-fifths (80.5%) of all deliveries were normal deliveries. Elective and emergency caesarean section rates were 3.1% and 11.5% respectively. There were 79 maternal deaths and 8 526 live births, giving a maternal mortality ratio of 927 maternal deaths per 100 000 live births. No antenatal care, parity, level of education, and mode of delivery were significantly associated with maternal mortality. Low maternal education, high parity, emergency caesarean delivery, and high risk patients risk independently predicted maternal mortality.

Conclusion

Meeting goal five of the MDGs remains a major challenge in Nigeria. Multi-sectoral approaches and focused political will are needed to revert the high maternal mortality.     

Effect of <Emphasis Type="Italic">Citrullus vulgaris</Emphasis> on some functional indices of selected tissues of Wistar rats

Citrullus vulgaris (watermelon) is a fruit with prophylactic and therapeutic potentials. In an attempt to maximize these potentials, the seed and rind are now often consumed together with the pulp. This study aimed at evaluating the implications of such consumption. Study involved the use of 35 Wistar rats grouped into seven with a control group administered distilled water, and the other groups administered varying concentrations of the pulp and whole fruit for 28 days. Alanine and aspartate aminotransferase (ALT, AST) were assayed in the serum and liver. Total protein of the serum and selected tissues was determined and malondialdehyde (MDA) level measured. Phytochemical screening revealed the presence of steroids, saponin, alkaloids, flavonoids, and terpenoids in both whole fruit and pulp. Significant increases (p < 0.05) were seen in the liver ALT levels while there was a decreased (p < 0.05) intestinal total protein in the treatment groups. No significant (p ? 0.05) difference was seen in the serum and pancreas MDA levels while an increased (p < 0.05) intestinal MDA level was observed. Increased liver ALT levels in all the treatment groups might be due to high glutamate levels of C. vulgaris. Decreased (p ? 0.05) intestinal total protein might be indicative of protein loss, while elevated (p < 0.05) intestinal MDA levels in the groups administered whole fruit is suggestive of a defect in absorption at the intestinal epithelium. Hence, whole fruit consumption of C. vulgaris should be done with caution as it has potential to cause intestinal oxidative stress.     

Effect of chloroquine on the urinary excretion of ciprofloxacin

Ciprofloxacin is an inexpensive antibacterial, whereas chloroquine is an inexpensive antimalarial. The coadministration of chloroquine and ciprofloxacin is easily encountered because both drugs are commonly prescribed to patients in the tropics. Five healthy male volunteers aged 19 to 31 years who were not taking any of the prescribed medications and who had no sensitivity to either ciprofloxacin or chloroquine each received 500 mg ciprofloxacin orally with 250 mL of water, and after a 2-week washout period, 500 mg ciprofloxacin plus 600 mg chloroquine was administered orally with 250 mL of water after providing informed consent. A urine sample (7 mL) was collected just before taking the drug at 8:00 AM representing 0 hour and continued afterward at 1, 2, 4, 8, 12, and 24 hours the next day. The samples were stored at -20 degrees C until analyzed. The minimum inhibitory concentrations by diffusion through agar technique were used for the assay of urine ciprofloxacin. The rate of ciprofloxacin excretion and cumulative urine ciprofloxacin were significantly increased. The coadministration of chloroquine increased the cumulative urinary concentration and excretion rate of ciprofloxacin.     

Some plasma pharmacokinetic parameters of isoniazid in the presence of a fluoroquinolone antibacterial agent.

The effects of ciprofloxacin (CP), a fluoroquinolone antibacterial agent, on the extent of absorption of isoniazid (INH) and on some of its pharmacokinetic parameters were investigated in six healthy female volunteers between the ages of 23 and 32 years. The presence of CP led to increase in the amount of INH and to a slight reduction in its peak plasma concentration (Cmax). There was a 1-hour increase in the time to attain Cmax (tmax) of INH, indicating absorption interaction between the two drugs. This absorption interaction was related to inhibition of cholinergic neurotransmission caused by CP, which is capable of inhibiting gastric motility, leading to a delay in gastric emptying. The rate of elimination (K) and plasma half-life (t1/2) of INH were not significantly affected (P = 0.05). The extent of absorption interaction that may have occurred (based on values of 24-hour values for area under the concentration curve, Cmax, Tmax, K, and t1/2) was considered to be of no therapeutic consequence, and the coadministration of the two drugs may be recommended in clinical practice.     

Ability of Activation Recovery Intervals to Assess Action Potential Duration During Acute No-Flow Ischemia in the In Situ Porcine Heart

Activation Recovery Intervals During No-Flow Ischemia . Introduction : The ability to assess transmural changes in action potential duration during acute no-flow ischemia is essential to an understanding of the tachyarrhythmias that occur in this setting. The purpose of this study was to determine if activation recovery intervals determined from unipolar electrograms would provide this information.
Methods and Results : We recorded simultaneously transmembrane action potentials and unipolar electrograms from sites located as closely together as possible in the center and at the lateral margin of the ischemic zone during acute no-flow ischemia and correlated the changes in activation recovery intervals obtained from the unipolar electrograms to the changes in action potential duration. We found that the activation recovery intervals provided an accurate measure of the changes in action potential duration during acute no-flow ischemia provided the electrograms had a well-defined, single negative component to the QRS complex with a maximum negative dV/dt > 10 V/sec and a single positive component to the T wave having a maximum positive dV/dt > 1.6 V/sec. Electrograms meeting these criteria comprised 90% of the electrograms recorded at the margin of the ischemic zone throughout 60 minutes of no-flow ischemia. In the center of the ischemic zone, 75% of the recorded electrograms met these criteria for the first 20 minutes of no-flow ischemia. Thereafter, the percentage declined and after 40 minutes of no-flow ischemia, none of the electrograms recorded in the center of the ischemic zone met these criteria.
Conclusion : Activation recovery intervals obtained from unipolar electrograms provide an accurate assessment of changes in action potential duration throughout the ischemic zone during acute no-flow ischemia, provided the characteristics of the electrograms meet specific predetermined criteria.